Due to the prevalence of thrombo-occlusive disease worldwide and the need for improved clinical treatments, ultrasound has been investigated, either alone or in combination with thrombolytic drugs, to improve recanalization in patients with this disease. A common thrombo-occlusive disease is ischemic stroke, whereby a clot within a vessel in the brain interrupts blood supply to the brain tissue. The occurrence of ischemic strokes is widespread, with greater than seven hundred thousand occurrences within the United States each year. Ischemic strokes occur as a result of a loss of blood supply to a portion of the brain which may be caused by thrombosis, embolism, or hypoperfusion. Ischemic strokes can lead to a variety of physical complications including permanent neurological damage and death. When brain tissue is deprived of oxygen for more than 60-90 seconds, the brain tissue loses its function; when brain tissue is deprived of oxygen for greater than three hours, irreversible injury results, leading to infarction. Thus, the ability to promptly treat a stroke is critical to the survival of a patient suffering from ischemic stroke.
Currently, treatment of ischemic stroke is generally limited to thrombolytic therapies, whereby a blood clot is broken up or dissolved. The American Heart Association recommends the administration of the thrombolytic agent tissue plasminogen activator (“t-PA”) for the treatment of ischemic strokes. However, this therapy possesses a number of drawbacks. For example, the administration of recombinant tissue plasminogen activator (“rt-PA”) is only moderately efficacious, resulting in a 30% greater chance of little or no disability in rt-PA treated patients as compared to a control at 3 months. Further, there is a 6.4% incidence of intracerebral hemorrhage in patients receiving this thrombolytic therapy. Thus, there is a substantial need for improved therapies to treat ischemic strokes.
The addition of ultrasound with clinically relevant intensities and frequencies has been shown to enhance the rate of some thrombolytic therapies in vitro. Moreover, a correlation has recently been observed between stable cavitation and ultrasound-enhanced thrombolysis. Cavitation is the formation, oscillation, and/or collapse of gaseous and/or vapor bubbles in a liquid due to an acoustic pressure field. In particular, stable cavitation results in emissions at subharmonic and ultraharmonic frequencies of the main excitation frequency.
Currently, methods of detecting cavitation include a variety of techniques, including acoustic cavitation detection and optical cavitation detection. However, these detection methods are also limited. Further, detection methods have yet to be employed to enhance stable cavitation during sonothrombolysis. Thus, additional methods and systems for ultrasound-mediated inducement, detection, and enhancement of stable cavitation are needed.